Perera et al. (2025)
- Authors: Krishani Dinali Perera, Paige Cameron, Tayyibah Sarwar, Simon R. Carding
- Institutes: Quadram Institute Bioscience, Norwich Research Park, Norwich, UK, Norwich Medical School, University of East Anglia, Norwich, UK
- Publisher: International Journal of Molecular Sciences
- Link: DOI
Summary
This review identifies a major blind spot in ME/CFS research by shifting the focus from blood-based testing to mucosal tissues like the gut and mouth. It suggests that many previous studies failed to find viral evidence simply because they were looking in the wrong place, as viruses often hide in mucosal reservoirs. This perspective provides a new framework for developing diagnostic tests and targeted therapies that address localized viral persistence rather than systemic infection.
What was researched?
This review investigated the potential role of persistent and reactivating viruses within mucosal tissues, such as the gastrointestinal and respiratory tracts, as a primary driver of ME/CFS.
Why was it researched?
Researchers sought to explain why blood-based viral studies in ME/CFS are often inconsistent despite most patients reporting a viral onset of their illness. Mucosal sites are primary entry points for pathogens and can serve as long-term reservoirs that the immune system in the blood may not fully reflect.
How was it researched?
The authors synthesized existing literature on viral detection in ME/CFS, specifically contrasting results from peripheral blood samples with those from mucosal sites like saliva and gut biopsies. They focused on common viruses such as Epstein-Barr virus (EBV), human herpesviruses (HHV-6), and human endogenous retroviruses (HERVs).
What has been found?
The findings indicate that mucosal tissues often harbor evidence of active or latent viruses even when those same viruses are undetectable in the blood. Specifically, evidence of HERVs and herpesvirus reactivation in saliva and gut biopsies suggests these sites may maintain the chronic inflammation and immune dysregulation seen in patients.
Discussion
A key limitation noted is the historical over-reliance on blood samples due to the invasive nature of mucosal biopsies. However, the authors argue that saliva and stool analysis offer less invasive windows into these critical mucosal environments.
Conclusion & Future Work
The study concludes that mucosal viruses are a likely ‘missing piece’ of the ME/CFS puzzle. Future research should prioritize multi-site sampling to better understand how localized viral persistence contributes to the systemic symptoms of the disease.